1. Field of the Invention
This invention relates to the methoxymethyl esters of certain substituted imidazolidinyl-3-methyl-3-cephem-4-carboxylic acids.
2. Description of the Prior Art
A. U.S. Pat. No. 3,714,146 discloses and claims, inter alia, 7-(D-2,2-dimethyl-5-oxo-4-phenyl-1-imidazolidinyl)-3-methyl-3-cephem-4-car boxylic acid [hereinafter referred to as hetacephalexin], having the formula ##STR2##
B. U.S. Pat. No. 3,489,752 and its reissue U.S. Pat. No. Re29,164 disclose and claim, inter alia, 7-[D-2,2-dimethyl-4-(p-hydroxyphenyl)-5-oxo-1-imidazolidinyl]-3-methyl-3-c ephem-4-carboxylic acid [hereinafter referred to as hetacefadroxil], having the formula ##STR3## The specification contains the very general statement "Also included are the easily hydrolyzed esters or amides of such acids which may be converted to the free acid form by chemical or enzymatic hydrolysis", but no such ester are exemplified or named.
C. U.S. Pat. No. 3,862,004 discloses and claims a process for the preparation of cephalosporins of the formula ##STR4## in which, inter alia, R may be phenyl or p-hydroxyphenyl, R.sup.1 may be hydrogen, n may be 1 and X may be methoxy. The process comprises enzymatic coupling of the appropriately substituted 7-amino-3-cephem compound with an acid of the formula R--CH(NH.sub.2)COOH.
When R.sup.1 is hydrogen, n is 1, R.sup.1 is methoxy and R is either phenyl or p-hydroxyphenyl, the compound is the methoxymethyl ester of cephalexin or the methoxymethyl ester of cefadroxil, respectively.
D. U.S. Pat. No. 3,996,236 discloses and claims the methoxymethyl ester of hetacillin, having the formula ##STR5##
E. French Published Patent Application No. 2,319,353 discloses and claims the methoxymethyl ester of the acetone adduct of amoxycillin, having the formula ##STR6##
F. The prior art contains numerous patents and publications directed to the preparation of deacetoxy cephalosporins (3-methyl-.DELTA..sup.3 -cephems) by ring enlargement reactions of penicillin sulfoxides. Some of this art make general statements to the effect that substantially any known penicillin side chain is suitable for use in the reaction. Alternatively, the art teaches that the resulting 3-methyl-.DELTA..sup.3 -cephem compound may be cleaved to produce 7-ADCA and then re-acylated with substantially any side chain. During the ring enlargement reaction the carboxyl group of the penicillin sulfoxide must be protected to prevent decarboxylation. This is often done by utilizing as ester of the penicillin sulfoxide--the product being the corresponding 3-methyl-.DELTA..sup.3 -cephem ester. Despite the voluminous prior art generated by numerous workers in this field, the instantly claimed compounds have not, to our knowledge, been described or disclosed in any of such prior art. The following patent is cited as representative of broad disclosure patents in the ring enlargement field.
U.S. Pat. No. 3,944,545 discloses a process for preparing substituted 3-methyl-3-cephem compounds via ring expansion of the corresponding penicillin sulfoxide. In its broad disclosure of suitable side chains of the formula ##STR7## R.sub.3 and R.sub.4 are defined as "an amino protecting group". Several broad sub-generic classes of side chains are given, including one in which R.sub.3 and R.sub.4, taken together with the nitrogen atom to which they are attached, may be "phthalimido, a cyclic imide moiety of a C.sub.3 -C.sub.12 dicarboxylic acid, 2,2-dimethyl-5-oxo-4-phenylimidazolidin-1-yl, 2,2-dimethyl-3-nitroso-5-oxo-4-phenylimidazolidin-1-yl, or the like". As to the carboxyl group, the patent discloses the group --COOR.sub.2 in which R.sub.2 "is a carboxy protecting group". A broad list of preferred carboxy protecting groups is given, but methoxymethyl is not encompassed thereby. The patent specifically discloses the preparation of the p-nitrobenzyl ester of 7-(2,2-dimethyl-5-oxo-4-phenylimidazolidin-1-yl)-3-methyl-3-cephem-4-carbo xylic acid.